Summary There is a narrow therapeutic range associated with the use of lithium which translates to the need for routine patient monitoring to maintain the proper levels of lithium. The current monitoring methods are not amenable to home use by a patient. This translates to an increasing need to provide patients with a reliable home-based testing tool for obtaining lithium ion levels so that they can conveniently and effectively monitor and manage their care. Testing lithium ion concentration in blood is extremely challenging due to the interference from sodium ions. This research program will overcome this problem and produce a prototypical device for lithium testing through the application of three coordinated strategies. Strategy 1 is to develop amperometry-type ion-selective electrodes and use the applied potentials to tune the selectivity. Strategy 2 is to develop 14-crown-4 derivatives with a high selectivity against sodium ions. Strategy 3 is to simultaneously measure lithium and sodium ion concentrations in a single test and correct the lithium concentration with the sodium measurement. An innovative research plan for integrating these strategies into a disposable single-use electrochemical test strip is deschbed, including measurement concept, method development, ionophore selection and synthesis, electrode design and fabrication protocols. Project Narrative: This research program will produce an amperometric ion-selective electrode based device for home-based blood lithium testing.